In recent years there has been considerable interest in the e4 allele of Apolipoprotein E (APOE), a genetic risk factor for Alzheimer's disease, as a risk factor for cognitive impairment in healthy aging. Recently, there has been growing recognition that women diagnosed with early stage breast cancer may experience cognitive problems as a consequence of adjuvant chemotherapy. In addition, research suggests that the presence of the e4 allele of APOE may also convey a disadvantage to the cognitive performance of breast cancer survivors. In the current proposal we examine cross-sectional differences and longitudinal changes in the cognitive functioning of a sample of breast cancer survivors and healthy controls as a function of APOE- e4 genotype. Specifically, we will assess APOE genotype of a group of breast cancer survivors who have been examined for over 3 years since the inception of treatment, as well as a matched sample of healthy controls who have been examined at a single measurement point. The specific aims are: 1) To compare cross-sectional differences in the cognitive performance of breast cancer survivors and healthy controls as a function of APOE-e4 genotype; 2) To examine longitudinal changes in cognitive performance among breast cancer survivors as a function of APOE-e4 genotype; and 3) To examine the role of cancer treatment-related and cardiovascular disease factors in the presence and severity of APOE-e4-related changes in cognitive performance among breast cancer survivors. Cognitive performance is indexed with multiple tests of episodic memory, attention, complex cognition, motor speed, and language. We predict that relative to healthy controls, the cognitive performance of breast cancer survivors will be poorer and breast cancer survivors who are APOE-e4 positive will perform most poorly. In terms of longitudinal changes, we predict that breast cancer survivors who are APOE-e4 positive will exhibit greater declines longitudinally, relative to non-e4 carriers. The results of the current proposal are relevant to attempts to describe factors that may predispose cancer survivors to negative cognitive outcomes after treatment. Identifying factors that may increase a person's risk of cognitive impairment following treatment for cancer is a great concern to public health. In the current proposal, we examine the potential of APOE-e4 genotype, known risk factor for Alzheimer's disease, to predispose breast cancer survivors for poor cognitive outcomes. [unreadable] [unreadable] [unreadable]